AKR1D1 and CFTR homozygous variants in an infant with combined bile acid synthesis defect and cystic fibrosis: first case report and management plan

Abstract Background Egypt is a large country with a very high rate of consanguineous marriage. The incidence of various recessive genetic disorders is expected to be much higher in Egyptian children. Case presentation In this study, we report on a 2-month-old Egyptian male presenting to our facility with jaundice, hepatomegaly, bleeding tendency, hyperammonemia and elevated alpha fetoprotein. This was rapidly followed by severe respiratory distress and persistent pneumonic patches. Since his parents were first cousins, a genetic etiology was highly suspected. Exome sequencing revealed two disease causing variants that were strongly associated with his phenotype: A novel homozygous variant in the AKR1D1 gene; NM_005989.4:c.458C > T;p.(Ala153Val) causing bile acid synthesis defect, congenital 2, with autosomal recessive mode of inheritance. The second is a known homozygous pathogenic variant in the CFTR gene; NM_000492.4: c.2988 + 1G > A causing cystic fibrosis, with autosomal recessive mode of inheritance. We further present the details of his phenotype and his management plan. Conclusions Dual genetic diagnosis appears to be more common than expected particularly in highly consanguineous families with complex genetic traits. Extensive genetic sequencing techniques as in exome and genome sequencing are essential for early diagnosis and proper management.